A Study to Evaluate Safety and Efficacy of ASP015K in Patients With Rheumatoid Arthritis (RA) Who Had an Inadequate Response to DMARDs

Astellas Pharma Inc509 enrolled

Overview

The objective of this study was to verify the superiority of ASP015K alone or in combination with disease-modifying antirheumatic drugs (DMARDs) over placebo in terms of efficacy in participants with rheumatoid arthritis (RA) who had an inadequate response to DMARDs

This was a multi-center, randomized, placebo-controlled, double-blind, parallel-group, confirmatory study to evaluate the efficacy and safety of ASP015K alone or in combination with DMARDs in participants with RA who had an inadequate response to DMARDs. Etanercept was also administered as the reference drug in an open-label manner. The study drug was orally administered once daily (QD) after breakfast for 52 weeks. Etanercept was administered subcutaneously QD for 52 weeks. At Week 12, participants in the placebo group were switched to ASP015K. The dose of ASP015K to be started at Week 12 for the placebo group was determined randomly at baseline in advance and switched in a blinded manner. Participants in ASP015K group or placebo groups who had completed the study were eligible for participation in an open-label extension study (015K-CL-RAJ2).

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Enrollment

509

Conditions

Rheumatoid Arthritis

Interventions

PeficitinibDRUG

oral

PlaceboDRUG

oral

EtanerceptBIOLOGICAL

subcutaneous injection

Eligibility

Sex: ALLMin age: 20 Years

Medical Language ↔ Plain English

Inclusion Criteria: * Subject has RA diagnosed according to the 1987 American College of Rheumatology (ACR) criteria or the 2010 American College of Rheumatology/European League against Rheumatism (ACR/EULAR) criteria * Subject who did not receive the following drugs, or received the drugs with stable dosage for at least 28 days prior to the baseline (start of treatment) for RA treatment: * Non-steroidal anti-inflammatory drugs (NSAIDs; excluding topical formulations), oral morphine or equivalent opioid analgesics (≤ 30 mg/day), acetaminophen, or oral corticosteroids (≤ 10 mg/day in prednisolone equivalent) * At screening subject has active RA as evidenced by both of the following: * ≥ 6 tender/painful joints (using 68-joint assessment) * ≥ 6 swollen joints (using 66-joint assessment) * CRP \> 0.50 mg/dL at screening * Subject meets the ACR 1991 Revised Criteria for the Classification of Global Functional Status in RA Class I, II or, III at screening. * Inadequate responder to (including subjects who were intolerant of) at least one DMARD administered for at least 90 days prior to screening Exclusion Criteria: * Subject has received a biologic DMARD within the specified period * Subject has received etanercept * Inadequate responder to at least 3 biologic DMARDs as determined by investigator/sub-investigator * Subject has received intra-articular, intravenous, intramuscular or endorectal (excluding suppositories for anal diseases) corticosteroid within 28 days prior to baseline * Subject has participated in any study of ASP015K and has received ASP015K or placebo * Subject has received other investigational drugs within 90 days or within 5 half-lives, whichever is longer, prior to baseline * Subject has received plasma exchange therapy within 60 days prior to baseline * Subject has undergone joint drainage, has received local anesthesia and nerve block, or has received articular cartilage protectant at the assessed joint within 28 days prior to baseline * Subject has undergone surgery and has residual effects in the assessed joints at the discretion of investigator/sub-investigator, or is scheduled to undergo surgery that may affect the study evaluation of the assessed joints at the discretion of investigator/sub-investigator * A diagnosis of inflammatory arthritis (psoriatic arthritis, ankylosing spondylitis, SLE, sarcoidosis, etc.) other than RA * Any of the following laboratory values at screening: * Hemoglobin \< 9.0 g/dL * Absolute neutrophil count \< 1000/μL * Absolute lymphocyte count \< 800/μL * Platelet count \< 75000/μL * ALT ≥ 2 ×ULN * AST ≥ 2 × ULN * Total bilirubin (TBL) ≥ 1.5 × ULN * Estimated GFR ≤ 40 mL/min as measured by the MDRD method * β-D-glucan \> ULN \[in case of Japan: ≥ 11 pg/mL\] * Positive HBs antigen, HBc antibody, HBs antibody or HBV-DNA quantitation (However, subject with negative HBs antigen and HBV-DNA quantitation, and positive HBc antibody and/or HBs antibody is eligible if HBV-DNA is monitored by HBV-DNA quantitation at every scheduled visit after initiation of study drug or reference drug administration.) * Positive HCV antibody * Subject has a history of or concurrent active tuberculosis (TB) * Subject has a history of or concurrent interstitial pneumonia and investigator/sub-investigator judges that it is inappropriate for the subject to participate in this study * Subject has a history of or concurrent malignant tumor (except for successfully treated basal cell carcinoma) * Subject has received live or live attenuated virus vaccination within 56 days prior to baseline. (Inactivated vaccines including influenza and pneumococcal vaccines are allowed.) * Subject has a history of or concurrent demyelinating disorders * Subject has any ongoing severe, progressive, or uncontrolled renal, hepatic, hematological, gastrointestinal, metabolic, endocrine, pulmonary, cardiac, neurological, infectious, or autoimmune disease except for RA (excluding Sjogren's syndrome and chronic thyroiditis), or any ongoing illness which would make the subject unsuitable for the study as determined by the investigator/sub-investigator * Subject has a history of clinically significant allergy. (Clinically significant allergy includes allergies such as systemic urticaria induced by specific antigens and drugs, anaphylaxis, and allergy associated with shock necessitating hospitalized treatment.) * Subject has concurrent cardiac failure, defined as NYHA classification Class III or higher, or a history of it * Subject has concurrent prolonged QT syndrome or a history of it. Subject has prolonged QT interval (defined as QTc ≥ 500 msec. Subject has QTc ≥ 500 msec at retest will be excluded) at screening * Subject has a history of positive HIV infection * Subject has congenital short QT syndrome or a history of it. Subject has shortened QT interval (defined as QTc \< 330 msec. Subject has QTc \< 330 msec at retest will be excluded) at screening.

Locations (153)

Outcomes

Primary Outcomes

Percentage of Participants With an American College of Rheumatology 20% (ACR20) C-Reactive Protein (CRP) Response at Week 12

The ACR20 response required that all criteria from (1) to (3) below be met. 1. Tender joint count (TJC) : ≥ 20% reduction compared with baseline. 2. Swollen joint count (SJC) : ≥ 20% reduction compared with baseline. 3. ≥ 20% improvement in 3 or more of the following 5 parameters compared with baseline (3) ≥ 20% improvement in 3 or more of the following 5 parameters compared with baseline: Subject's assessment of pain, Subject's Global Assessment of Arthritis (SGA), Physician's Global Assessment of Arthritis (PGA), Health Assessment Questionnaire - Disability Index (HAQ-DI), C-Reactive Protein (CRP).

Time frame: Baseline and Week 12/early termination (ET)

Secondary Outcomes

Percentage of Participants With an ACR20-CRP Response Through Week 52

The ACR20 response required that all criteria from (1) to (3) below be met. 1. TJC : ≥ 20% reduction compared with baseline. 2. SJC : ≥ 20% reduction compared with baseline. 3. ≥ 20% improvement in 3 or more of the following 5 parameters compared with baseline: Subject's assessment of pain, SGA, PGA, HAQ-DI, CRP.

Time frame: Baseline and Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52

Percentage of Participants With an American College of Rheumatology 50% (ACR50)-CRP Response at Week 12

The ACR50 response required that all criteria from (1) to (3) below be met. 1. TJC : ≥ 50% reduction compared with baseline. 2. SJC : ≥ 50% reduction compared with baseline. 3. ≥ 50% improvement in 3 or more of the following 5 parameters compared with baseline: Subject's assessment of pain, SGA, PGA, HAQ-DI, CRP.

Time frame: Baseline and Week 12/ET

Percentage of Participants With an ACR50-CRP Response Through Week 52

Data from ClinicalTrials.gov

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JP00037

Nagoya, Aichi-ken, Japan

JP00109

Nagoya, Aichi-ken, Japan

JP00130

Nagoya, Aichi-ken, Japan

JP00066

Okazaki, Aichi-ken, Japan

JP00140

Toyoake, Aichi-ken, Japan

JP00108

Toyohashi, Aichi-ken, Japan

JP00156

Toyota, Aichi-ken, Japan

JP00068

Yatomi, Aichi-ken, Japan

JP00102

Kamagaya, Chiba, Japan

JP00127

Matsudo, Chiba, Japan

...and 143 more locations

Time frame: Baseline and Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52

Percentage of Participants With an American College of Rheumatology 70% (ACR70)-CRP Response at Week 12

The ACR70 response required that all criteria from (1) to (3) below be met. 1. TJC : ≥ 70% reduction compared with baseline. 2. SJC : ≥ 70% reduction compared with baseline. 3. ≥ 70% improvement in 3 or more of the following 5 parameters compared with baseline: Subject's assessment of pain, SGA, PGA, HAQ-DI, CRP.

Time frame: Baseline and Week 12/ET

Percentage of Participants With an ACR70-CRP Response Through Week 52

Time frame: Baseline and Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52

Change From Baseline in Disease Activity Score (DAS) 28-CRP at Week 12

DAS28-CRP response consisted of following parameters: TJC (28 joints), SJC (28 joints), CRP, SGA, and calculated according to below description. DAS28 = 0.56√(TJC) + 0.28√(SJC) + 0.36 ln (CRP + 1) + 0.014 × SGA + 0.96. DAS28-CRP scores range from 0.96 to approximately 10. Higher DAS28 score indicated greater disease activity.

Time frame: Baseline and Week 12/ET

Change From Baseline DAS28-CRP Through Week 52

Time frame: Baseline and Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52

Change From Baseline in DAS28-Erythrocyte Sedimentation Rate (ESR) at Week 12

DAS28-ESR response consisted of following parameters: TJC (28 joints), SJC (28 joints), ESR, SGA , and calculated according to below description. DAS28 = 0.56√(TJC) + 0.28√(SJC) + 0.70 ln ESR + 0.014 × SGA. DAS28-ESR scores range from 0 to approximately 10. Higher DAS28 score indicated greater disease activity.

Time frame: Baseline and Week 12/ET

Change From Baseline in DAS28-ESR Through Week 52

Time frame: Baseline and Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52

Change From Baseline in TJC (68 Joints) at Week 12

The following 68 joints subjects to assessment were examined for tender joints and the location was confirmed. Higher TJC68 indicated greater disease activity. Temporomandibular joints (2), sternoclavicular joints (2), acromioclavicular joints (2), shoulder joints (2), elbow joints (2), wrist joints (2), distal interphalangeal joints (8), proximal interphalangeal joints of both hands (10), metacarpophalangeal joints (10), hip joints (2), knee joints (2), ankle joints (2), tarsal bones (2), metatarsophalangeal joints (10), interphalangeal joint joints of toes (2), proximal interphalangeal joints of both feet (8).

Time frame: Baseline and Week 12/ET

Change From Baseline in TJC (68 Joints) Through Week 52

Time frame: Baseline and Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52

Change From Baseline in Swollen Joint Count (SJC) (66 Joints) at Week 12

The following 66 joints subjects to assessment were examined for swollen joints and the location was confirmed. Higher SJC66 indicated greater disease activity. Temporomandibular joints (2), sternoclavicular joints (2), acromioclavicular joints (2), shoulder joints (2), elbow joints (2), wrist joints (2), distal interphalangeal joints (8), proximal interphalangeal joints of both hands (10), metacarpophalangeal joints (10), knee joints (2), ankle joints (2), tarsal bones (2), metatarsophalangeal joints (10), interphalangeal joint joints of toes (2), proximal interphalangeal joints of both feet (8).

Time frame: Baseline and Week 12/ET

Change From Baseline in SJC (66 Joints) Through Week 52

Time frame: Baseline and Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52

Percentage of Participants Achieving DAS28-CRP < 2.6 at Week 12

DAS28-CRP response consisted of following parameters: TJC (28 joints), SJC (28 joints), CRP, SGA, and calculated according to below description. DAS28 = 0.56√(TJC) + 0.28√(SJC) + 0.36 ln (CRP + 1) + 0.014 × SGA + 0.96. DAS28-CRP scores range from 0.96 to approximately 10. If the DAS28 score was less than 2.6, the participant was considered to be in DAS28 remission.

Time frame: Baseline and Week 12/ET

Percentage of Participants Achieving DAS28-CRP < 2.6 Through Week 52

DAS28-CRP response consisted of following parameters: TJC (28 joints), SJC (28 joints), CRP, SGA, and calculated according to below description. DAS28 = 0.56√(TJC) + 0.28√(SJC) + 0.36 ln (CRP + 1) + 0.014 × SGA + 0.96. DAS28-CRP scores range from 0.96 to approximately 10. If the DAS28 score was less than 2.6, the participant was considered to be in DAS28 remission.

Time frame: Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52

Percentage of Participants Achieving DAS28-ESR < 2.6 at Week 12

DAS28-ESR response consisted of following parameters: TJC (28 joints), SJC (28 joints), ESR, SGA , and calculated according to below description. DAS28 = 0.56√(TJC) + 0.28√(SJC) + 0.70 ln ESR + 0.014 × SGA. DAS28-ESR scores range from 0 to approximately 10. If the DAS28 score was less than 2.6, the participant was considered to be in DAS28 remission.

Time frame: Week 12/ET

Percentage of Participants Achieving DAS28-ESR < 2.6 Through Week 52

DAS28-ESR response consisted of following parameters: TJC (28 joints), SJC (28 joints), ESR, SGA , and calculated according to below description. DAS28 = 0.56√(TJC) + 0.28√(SJC) + 0.70 ln ESR + 0.014 × SGA. DAS28-ESR scores range from 0 to approximately 10. If the DAS28 score was less than 2.6, the participant was considered to be in DAS28 remission.

Time frame: Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52

Percentage of Participants Achieving DAS28-CRP <= 3.2 at Week 12

DAS28-CRP response consisted of following parameters: TJC (28 joints), SJC (28 joints), CRP, SGA, and calculated according to below description. DAS28 = 0.56√(TJC) + 0.28√(SJC) + 0.36 ln (CRP + 1) + 0.014 × SGA + 0.96. DAS28-CRP scores range from 0.96 to approximately 10. DAS28 score of less than or equal to 3.2 was considered to be low disease activity.

Time frame: Week 12/ET

Percentage of Participants Achieving DAS28-CRP <= 3.2 Through Week 52

DAS28-CRP response consisted of following parameters: TJC (28 joints), SJC (28 joints), CRP, SGA, and calculated according to below description. DAS28 = 0.56√(TJC) + 0.28√(SJC) + 0.36 ln (CRP + 1) + 0.014 × SGA + 0.96. DAS28-CRP scores range from 0.96 to approximately 10. DAS28 score of less than or equal to 3.2 was considered to be low disease activity.

Time frame: Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52

Percentage of Participants Achieving DAS28-ESR <= 3.2 at Week 12

DAS28-ESR response consisted of following parameters: TJC (28 joints), SJC (28 joints), ESR, SGA , and calculated according to below description. DAS28 = 0.56√(TJC) + 0.28√(SJC) + 0.70 ln ESR + 0.014 × SGA. DAS28-ESR scores range from 0 to approximately 10. DAS28 score of less than or equal to 3.2 was considered to be low disease activity.

Time frame: Week 12/ET

Percentage of Participants Achieving DAS28-ESR <= 3.2 Through Week 52

DAS28-ESR response consisted of following parameters: TJC (28 joints), SJC (28 joints), ESR, SGA , and calculated according to below description. DAS28 = 0.56√(TJC) + 0.28√(SJC) + 0.70 ln ESR + 0.014 × SGA. DAS28-ESR scores range from 0 to approximately 10. DAS28 score of less than or equal to 3.2 was considered to be low disease activity.

Time frame: Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52

Change From Baseline in CRP at Week 12

Higher CRP indicates greater disease activity.

Time frame: Baseline and Week 12/ET

Change From Baseline in CRP Through Week 52

Higher CRP indicates greater disease activity.

Time frame: Baseline and Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52

Change From Baseline in ESR at Week 12

Higher ESR indicates greater disease activity.

Time frame: Baseline and Week 12/ET

Change From Baseline in ESR Through Week 52

Higher ESR indicates greater disease activity.

Time frame: Baseline and Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52

Percentage of Participants With a European League Against Rheumatism (EULAR) Good Response Using DAS28-CRP at Week 12

Good response was defined as DAS28 after treatment ≤ 3.2 and improvement from baseline \> 1.2.

Time frame: Week 12/ET

Percentage of Participants With a EULAR Good Response Using DAS28-CRP Through Week 52

Good response was defined as DAS28 after treatment ≤ 3.2 and improvement from baseline \> 1.2.

Time frame: Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52

Percentage of Participants With a Good or Moderate EULAR Response Using DAS28-CRP at Week 12

Good and moderate response was defined as DAS28 after treatment ≤ 5.1 and improvement from baseline \> 0.6, or DAS28 after treatment \> 5.1 and improvement from baseline \> 1.2.

Time frame: Week 12/ET

Percentage of Participants With a Good or Moderate EULAR Response Using DAS28-CRP Through Week 52

Good and moderate response was defined as DAS28 after treatment ≤ 5.1 and improvement from baseline \> 0.6, or DAS28 after treatment \> 5.1 and improvement from baseline \> 1.2.

Time frame: Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52

Percentage of Participants With a Good EULAR Response Using DAS28-ESR at Week 12

Good response was defined as DAS28 after treatment ≤ 3.2 and improvement from baseline \> 1.2.

Time frame: Week 12/ET

Percentage of Participants With a Good EULAR Response Using DAS28-ESR Through Week 52

Good response was defined as DAS28 after treatment ≤ 3.2 and improvement from baseline \> 1.2.

Time frame: Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52

Percentage of Participants With a Good or Moderate EULAR Response Using DAS28-ESR at Week 12

Good and moderate response was defined as DAS28 after treatment ≤ 5.1 and improvement from baseline \> 0.6, or DAS28 after treatment \> 5.1 and improvement from baseline \> 1.2.

Time frame: Week 12/ET

Percentage of Participants With a Good or Moderate EULAR Response Using DAS28-ESR Through Week 52

Good and moderate response was defined as DAS28 after treatment ≤ 5.1 and improvement from baseline \> 0.6, or DAS28 after treatment \> 5.1 and improvement from baseline \> 1.2.

Time frame: Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52

Percentage of Participants Achieving ACR / EULAR Remission at Week 12

ACR/EULAR Remission was defined as TJC (68 joints) ≤ 1, SJC (66 joints) ≤ 1, CRP ≤ 1 mg/dL, and subject's global assessment of arthritis ≤ 1 cm (on a visual analog scale (VAS) of 0 - 100 mm). Statistical analysis of treatment difference vs placebo was not estimable for either peficitinib 100 mg or peficitinib 150 mg reporting groups.

Time frame: Week 12/ET

Percentage of Participants Achieving ACR / EULAR Remission Through Week 52

ACR/EULAR Remission was defined as TJC (68 joints) ≤ 1, SJC (66 joints) ≤ 1, CRP ≤ 1 mg/dL, and subject's global assessment of arthritis ≤ 1 cm (on a VAS of 0 - 100 mm).

Time frame: Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52

Percentage of Participants Achieving Simplified Disease Activity Index (SDAI) Remission at Week 12

SDAI score consisted of following parameters: TJC (28 joints), SJC (28 joints), SGA, PGA, CRP (mg/dL), and calculated according to below description. SDAI = TJC + SJC + SGA + PGA + CRP. SDAI Remission was defined as SDAI score ≤ 3.3. Statistical analysis of treatment difference vs placebo was not estimable for either peficitinib 100 mg or peficitinib 150 mg reporting groups.

Time frame: Week 12/ET

Percentage of Participants Achieving SDAI Remission Through Week 52

Time frame: Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52

Change From Baseline in SDAI Score at Week 12

SDAI score consisted of following parameters: TJC (28 joints), SJC (28 joints), SGA, PGA, CRP (mg/dL), and calculated according to below description. SDAI = TJC + SJC + SGA + PGA + CRP. The SDAI score ranges from 0 to approximately 86. Higher SDAI indicates greater disease activity.

Time frame: Baseline and Week 12/ET

Change From Baseline in SDAI Score Through Week 52

SDAI score consisted of following parameters: TJC (28 joints), SJC (28 joints), SGA, PGA, CRP (mg/dL), and calculated according to below description. SDAI = TJC + SJC + SGA + PGA + CRP. The SDAI score ranges from 0 to approximately 86. Higher SDAI indicates greater disease activity.

Time frame: Baseline and Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52

Percentage of Participants Achieving Clinical Disease Activity Index (CDAI) Score <= 2.8 at Week 12

CDAI score consisted of following parameters: TJC (28 joints), SJC (28 joints), SGA, PGA, and calculated according to below description. CDAI = TJC + SJC + SGA + PGA. CDAI. Remission was defined as CDAI score ≤ 2.8. Statistical analysis of treatment difference vs placebo was not estimable for either peficitinib 100 mg or peficitinib 150 mg reporting groups.

Time frame: Week 12/ET

Percentage of Participants Achieving CDAI Score <= 2.8 Through Week 52

Time frame: Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52

Change From Baseline in CDAI Score at Week 12

CDAI score consisted of following parameters: TJC (28 joints), SJC (28 joints), SGA, PGA, and calculated according to below description. CDAI = TJC + SJC + SGA + PGA. The CDAI score ranges from 0 to approximately 76. Higher CDAI indicates greater disease activity.

Time frame: Baseline and Week 12/ET

Change From Baseline in CDAI Score Through Week 52

Time frame: Baseline and Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52

Change From Baseline in Physician's Global Assessment of Arthritis (PGA) at Week 12

The investigator assessed the participants' disease activity on a VAS of 0-100 mm on the physician assessment table. Higher PGA (100 mm VAS) scores indicate greater activity impairment.

Time frame: Baseline and Week 12/ET

Change From Baseline in PGA Through Week 52

The investigator assessed the participants' disease activity on a VAS of 0-100 mm on the physician assessment table. Higher PGA (100 mm VAS) scores indicate greater activity impairment.

Time frame: Baseline and Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52

Change From Baseline in Subject's SGA at Week 12

The participant assessed his/her own disease activity on a VAS of 0-100 mm on the questionnaire form. Higher SGA (100 mm VAS) scores indicate greater activity impairment.

Time frame: Baseline and Week 12/ET

Change From Baseline in SGA Through Week 52

The participant assessed his/her own disease activity on a VAS of 0-100 mm on the questionnaire form. Higher SGA (100 mm VAS) scores indicate greater activity impairment.

Time frame: Baseline and Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52

Change From Baseline in Subject's Assessment of Pain at Week 12

The participant assessed his/her own pain severity on a VAS from 0-100 mm on the questionnaire form. Higher SGA of pain (100 mm VAS) scores indicate greater activity pain.

Time frame: Baseline and Week 12/ET

Change From Baseline in Subject's Assessment of Pain Through Week 52

The participant assessed his/her own pain severity on a VAS from 0-100 mm on the questionnaire form. Higher SGA of pain (100 mm VAS) scores indicate greater activity pain.

Time frame: Baseline and Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52

Number of Participants Who Withdrew Due to Lack of Efficacy

The number of participants who withdrew due to lack of efficacy up to week 12 was calculated.

Time frame: Up to week 12

Change From Baseline in Health Assessment Questionnaire - Disability Index (HAQ-DI) at Week 12

The HAQ-DI (range 0 - 3) was composed of 20 items in 8 categories (Dressing and Grooming, Arising, Eating, Walking, Hygiene, Reach, Grip, and Activities). Each category has at least two questions. Within each category, participants reported the amount of difficulty they have in performing the specific question items. Higher HAQ-DI score indicates greater disease activity.

Time frame: Baseline and Week 12/ET

Change From Baseline in HAQ-DI Through Week 52

Time frame: Baseline and Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52

Change From Baseline in Short Form Health Survey - 36 Questions, Version 2 (SF-36v2) Physical Component Summary Score at Week 12

The SF-36v2 was scored for the 8 subscales (each range: 0-100 scale): 1. physical functioning, 2. role physical, 3. bodily pain, 4. general health, 5. vitality, 6. social functioning, 7. role-emotional, and 8. mental health. Physical Component Summary Score, Mental Component Summary Score and Roll/Social Component Summary Score were calculated based on the 2007 General Japanese Population Means and Standard Deviations and coefficient. Component summary measures had means of 50 in 2007 General Japanese Population and deviation was expressed by the scale of 10. Higher score indicated better health state.

Time frame: Baseline and Week 12/ET

Change From Baseline in SF-36v2 Physical Component Summary Score Through Week 52

Time frame: Baseline and Week 4, 8, 12, 28, and 52

Change From Baseline in SF-36v2 Mental Component Summary Score at Week 12

Time frame: Baseline and Week 12/ET

Change From Baseline in SF-36v2 Mental Component Summary Score Through Week 52

Time frame: Baseline and Week 4, 8, 12, 28, and 52

Change From Baseline in SF-36v2 Role/Social Component Summary Score at Week 12

Time frame: Baseline and Week 12/ET

Change From Baseline in SF-36v2 Role/Social Component Summary Score Through Week 52

Time frame: Baseline and Week 4, 8, 12, 28, and 52

Change From Baseline in Work Productivity and Activity Impairment Questionnaire (WPAI) Percent Work Time Missed at Week 12

WPAI consisted of 6 questions (Q1=Employment status; Q2=Hours absent from work due to the rheumatoid arthritis; Q3=Hours absent from work due to other reasons; Q4=Hours actually worked; Q5=Impact of the rheumatoid arthritis on productivity while working; Q6=Impact of the rheumatoid arthritis on productivity while doing regular daily activities other than work) and a 1-week recall period. Higher WPAI scores indicate greater activity impairment. Multiply scores by 100 to express in percentages. Percent work time missed due to problem: Q2/(Q2+Q4).

Time frame: Baseline and Week 12/ET

Change From Baseline in WPAI Percent Work Time Missed Through Week 52

Time frame: Baseline and Week 4, 8, 12, 28, and 52

Change From Baseline in WPAI Percent Impairment While Working at Week 12

Time frame: Baseline and Week 12/ET

Change From Baseline in WPAI Percent Impairment While Working Through Week 52

Time frame: Baseline and Week 4, 8, 12, 28, and 52

Change From Baseline in Percent Overall Work Impairment at Week 12

Time frame: Baseline and Week 12/ET

Change From Baseline in WPAI Percent Overall Work Impairment Through Week 52

Time frame: Baseline and Week 4, 8, 12, 28, and 52

Change From Baseline in WPAI Percent Activity Impairment at Week 12

Time frame: Baseline and Week 12/ET

Change From Baseline in WPAI Percent Activity Impairment Through Week 52

Time frame: Baseline and Week 4, 8, 12, 28, and 52

Number of Participants With Adverse Events During the First 12 Weeks

Treatment-emergent adverse events (TEAEs) were defined as any AE that started or worsened in severity after initial dose of study drug or reference drug through week 52 or withdrawal. TEAEs were summarized using MedDRA (Version 11.1) by System Organ Class (SOC) and Preferred Term (PT). Participants reporting more than 1 AE for a given MedDRA PT were counted only once for that term. Participants reporting more than 1 AE within a SOC were counted only once for the SOC total. Based on National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) grade: grade 3 = severe or medically significant, grade 4 = life threatening, grade 5 = death related to AE.

Time frame: Week 0 to Week 12

Number of Participants With Adverse Events From Week 12

Treatment-emergent adverse events (TEAEs) were defined as any AE that started or worsened in severity after initial dose of study drug or reference drug through week 52 or withdrawal. TEAEs were summarized using MedDRA (Version 11.1) by SOC and PT. Participants reporting more than 1 AE for a given MedDRA PT were counted only once for that term. Participants reporting more than 1 AE within a SOC were counted only once for the SOC total. Based on National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) grade: grade 3 = severe or medically significant, grade 4 = life threatening, grade 5 = death related to AE.

Time frame: Week 12 to week 52, plus 28 days after the week 52 visit for participants who did not enroll in the extension study